Musculoskeletal disorders and psychosocial factors at work : Effects of a participatory ergonomics intervention in a cluster randomized controlled trial

This study examined the efficacy of a participatory ergonomics intervention in preventing musculoskeletal disorders (MSDs) and changing unsatisfactory psychosocial working conditions among municipal kitchen workers. The occurrence of multiple-site musculoskeletal pain (MSP) and associations between MSP and psychosocial factors at work over time were studied secondarily. A cluster randomized controlled trial was conducted during 2002-2005 in 119 municipal kitchens with 504 workers. The kitchens were randomized to an intervention (n = 59) and control (n = 60) group. The intervention lasted 11 to 14 months. The workers identified strenuous work tasks and sought solutions for decreasing physical and mental workload. The main outcomes were the occurrence of and trouble caused by musculoskeletal pain in seven anatomical sites, local musculoskeletal fatigue after work, and musculoskeletal sick leaves. Psychosocial factors at work (job control, skill discretion, co-worker relationships, supervisor support, mental strenuousness of work, hurry, job satisfaction) and mental stress were studied as intermediate outcomes of the intervention. Questionnaire data were collected at three months intervals during the intervention and the one-year post-intervention follow-up. Response rates varied between 92 % and 99 %. In total, 402 ergonomic changes were implemented. In the control group, 80 changes were spontaneously implemented within normal activity. The intervention did not reduce perceived physical workload and no systematic differences in any health outcomes were found between the intervention and control groups during the intervention or during the one-year follow-up. The results suggest that the intervention as studied in the present trial was not more effective in reducing perceived physical workload or preventing MSDs compared with no such intervention. Little previous evidence of the effectiveness of ergonomics interventions in preventing MSDs exists. The effects on psychosocial factors at work were adverse, especially in the two of the participating cities where re-organization of foodservices timed simultaneously with the intervention. If organizational reforms at workplace are expected to occur, the execution of other workplace interventions at the same time should be avoided. The co-occurrence of musculoskeletal pain at several sites is observed to be more common than pain at single anatomical sites. However, the risk factors of MSP are largely unknown. This study showed that at baseline, 73 % of the women reported pain in at least two, 36 % in four or more, and 10 % in six to seven sites. The seven pain symptoms occurred in over 80 different combinations. When co-occurrence of pain was studied in three larger anatomical areas (neck/low back, upper limbs, lower limbs), concurrent pain in all three areas was the most common combination (36 %). The 3-month prevalence of MSP (≥ 3 of seven sites) varied between 50 % and 61 % during the two-year follow-up period. Psychosocial factors at work and mental stress were strong predictors for MSP over time and, vice versa, MSP predicted psychosocial factors at work and mental stress. The reciprocality of the relationships implies either two mutually dependent processes in time, or some shared common underlying factor(s).

Synthesis, Reactivity and Biological Activity of 17β-HSD1 Inhibitors Based on a Thieno[2,3-d]pryrimidin-4(3H)-one Core

Breast cancer is the most common cancer in women in Western countries. In the early stages of development most breast cancers are hormone-dependent, and estrogens, especially estradiol, have a pivotal role in their development and progression. One approach to the treatment of hormone-dependent breast cancers is to block the formation of the active estrogens by inhibiting the action of the steroid metabolising enzymes. 17beta-Hydroxysteroid dehydrogenase type 1 (17beta-HSD1) is a key enzyme in the biosynthesis of estradiol, the most potent female sex hormone. The 17beta-HSD1 enzyme catalyses the final step and converts estrone into the biologically active estradiol. Blocking 17beta-HSD1 activity with a specific enzyme inhibitor could provide a means to reduce circulating and tumour estradiol levels and thus promote tumour regression. In recent years 17beta-HSD1 has been recognised as an important drug target. Some inhibitors of 17beta-HSD1 have been reported, however, there are no inhibitors on the market nor have clinical trials been announced. The majority of known 17beta-HSD1 inhibitors are based on steroidal structures, while relatively little has been reported on non-steroidal inhibitors. As compared with 17beta-HSD1 inhibitors based on steroidal structures, non-steroidal compounds could have advantages of synthetic accessibility, drug-likeness, selectivity and non-estrogenicity. This study describes the synthesis of large group of novel 17beta-HSD1 inhibitors based on a non-steroidal thieno[2,3-d]pyrimidin-4(3H)-one core. An efficient synthesis route was developed for the lead compound and subsequently employed in the synthesis of thieno[2,3-d]pyrimidin-4(3H)-one based molecule library. The biological activities and binding of these inhibitors to 17beta-HSD1 and, finally, the quantitative structure activity relationship (QSAR) model are also reported. In this study, several potent and selective 17beta-HSD1 inhibitors without estrogenic activity were identified. This establishment of a novel class of inhibitors is a progressive achievement in 17beta-HSD1 inhibitor development. Furthermore, the 3D-QSAR model, constructed on the basis of this study, offers a powerful tool for future 17beta-HSD1 inhibitor development. As part of the fundamental science underpinning this research, the chemical reactivity of fused (di)cycloalkeno thieno[2,3-d]pyrimidin-4(3H)-ones with electrophilic reagents, i.e. Vilsmeier reagent and dimethylformamide dimethylacetal, was investigated. These findings resulted in a revision of the reaction mechanism of Vilsmeier haloformylation and further contributed to understanding the chemical reactivity of this compound class. This study revealed that the reactivity is dependent upon a stereoelectronic effect arising from different ring conformations.

Effects of 17α-ethinyl estradiol on the mating system of the sand goby (Pomatoschistus minutus)

In aquatic environments, endocrine disrupting chemicals (EDCs) that interfere with the endocrinology of males and females form a threat to the maintenance of populations. EDCs are a diverse group of natural and manmade chemicals that already at very low concentrations (at nanogram levels) can have severe effects on reproduction by individuals, e.g. complete sex reversal, feminisation of males, impaired reproduction even resulting in near extinction of populations. With regard to fish, despite the extensive literature on physiological effects of EDCs, very little is known about potential population-level effects. In this thesis, I examined how 17α-ethinyl estradiol (EE2), a synthetic estrogen used in oral contraceptive pills, affects the reproductive behaviour of a marine fish, the sand goby (Pomatoschistus minutus). The aims were fourfold. First, I investigated how exposure to EE2 affects courtship and parental care of sand goby males. Secondly, I looked at effects on the mating system and sexual selection. In the third study, I observed the effects of exposure in a social context where exposed males had to compete with non-exposed males for resources and mates. Finally, I studied the effects of exposure on male-male competition and male aggressive behaviour. This work revealed that EE2 exposure impairs the ability of males to acquire and defend a nest, as well as diminishes the attractiveness of males to females by decreasing their courtship and aggressive behaviour. These effects are harmful for a male whose reproductive success is determined by the ability to compete for limited resources and to attract mates. Furthermore, this thesis showed that selection on male size was relaxed after EE2 exposure and male size had a smaller effect on mating success. These effects can be of a profound nature as they interfere with sexual selection, and may in the long run lead to the loss of traits maintained through sexual selection. The thesis shows that an exposure to environmentally relevant levels of EE2 clearly reduces the chances of individuals to reproduce successfully. Furthermore, it strongly suggests that several types of biomarkers should be used to detect and assess the effects of EDC exposure because severe behavioural effects can sometimes be seen before effects are detectable at the molecular or morphometric level. Behavioural assays should be considered an important complementary tool for the standard ecotoxicological assays because observed behavioural changes have direct and negative effects on fitness, while the connection between changes in molecular expression and fitness may be less obvious.

Designing Creativity Through Clusters - A periodisation of cluster discourse

The thesis focuses on one of the most dominant articulations of the relation between geographical place and development, clusters - internationally competing place-bound economic system of production in related industries. The dominant articulation of cluster discourse represents the subnational region as a system of production, and as a means for competitiveness for Western countries. Its reproduction in theories has become one of the most prolific exports of economic geography to other disciplines and for policymaking. By analysing cluster discourse the thesis traces how the languages and processes of globalization have over time altered the understandings of the relation between geographical place and the economy. It shows how in its latest incarnation of the cluster discourse, the language of mainstream economics is combined with ‘softer’ elements (e.g. community, learning, creativity) in the economic geographic discourse. This is typical for the idea of soft capitalism, wherein it is assumed that economic success emanates from soft characteristics, such as knowledge, learning and creativity, rather than straightforward technological or cost advantages. A reoccurring critique against the dominant understanding of the relationship between competitiveness and regions, as articulated in cluster discourse, has pinpointed the perspective’s inability to reconcile the respective and reciprocal roles of local standard of living with firm competitiveness. The thesis traces how such critique is increasingly appropriated through the fusion of the economic, social and cultural landscape into the language of capitalism. It shows how cluster discourse has appropriated its critique, by focusing on creativity, with its strong associations to arts, individual artists and the cultural sphere in general, while predominantly creating its meaning in relation to competitiveness. The thesis consists of six essays that each outlines the development of the cluster discourse. The essays show how meaning systems and strategies are created, accepted and naturalized in cluster discourse, how this affects individuals, the economic landscape and society at large, as well as showing which understandings are marginalized in the process. The thesis argues that clusters are a) inseparable from ideology and politics and b) they are the result of purposeful social practice. It calls for increased reflexivity within corporate and economic geographic research on clusters, and underlines the importance of placing issues of power at the centre of analysis.

Käsitteellisestä ruumiilliseen, sitaatiosta paikkaan - maalaustaide ja nykytaiteen historia

The dissertation "From Conceptual to Corporeal, from Quotation to Site: Painting and History of Contemporary Art" explores the state of painting in contemporary art and art theory since the 1960s. The purpose of the study is to re-consider the dominant "end of painting" -narrative in contemporary art history, which goes back to the modernist ideology of painting as a reductive, medium-specific form of art. Drawing on Michel Foucault´s concepts of discursive formation and archive, as well as Jean-Luc Nancy´s post-phenomenological philosophy on corporeality, I suggest that contemporary painting can be redefined as a discursive-sensuous practice. Instead of seeing painting as obsolete or over as an avantgarde art genre, I show that there have been alternative, neo-avantgardist ways of defining painting since the end of the 1960s, such as French artist Daniel Buren´s early writings on painting as "theoretical practice". Consequently, the tendency of the canonical Anglo-American contemporary art narratives to underestimate the historical and institutional codes of art can be questioned. This tendency can be seen, for example, in Rosalind Krauss´s influential theory on index. The study also reflects the relations between conceptual art and painting since the 1960s and maps recent theories of painting, which re-examine the genre´s possibilities after the modernist rhetoric. Concepts of "flatbed", "painting in the extended field", "as painting" and so on are compared critically with the idea of painting as discursive practice. It is also shown that the issues in painting arise from the contemporary critical art debate while the dematerialisation paradigm of conceptual art has dissolved. The study focuses on the corporeal-material-sensuous -cluster of meanings attached to painting and searches for its avantgardist possibilities as redefined by postfeminist and post-phenomenological discourse. The ideas of hierarchy of the senses and synesthesia are developed within the framework of Jean-Luc Nancy´s and Luce Irigaray´s thought. The parameters for the study have been Finnish painting from 1990 to 2002. On the Finnish art scene there has been no "end of painting" ideology, strictly speaking. The mythology and medium-specificity of modernism have been deconstructed since the mid-1980s, but "the archive" of painting, like themes of abstraction, formalism and synesthesia have been re-worked by the discursive practice of painting, for example, in the works of Nina Roos, Tarja Pitkänen-Walter and Jussi Niva.

"Secoituxesta järjettömäin luondocappalden canssa" : Perversiot, oikeuselämä ja kansankulttuuri 1700-luvun Suomessa

Bestiality was in the 18th century a more difficult problem in terms of criminal policy in Sweden and Finland than in any other Christian country in any other period. In the legal history of deviant sexuality, the phenomenon was uniquely widespread by international comparison. The number of court cases per capita in Finland was even higher than in Sweden. The authorities classified bestiality among the most serious crimes and a deadly sin. The Court of Appeal in Turku opted for an independent line and was clearly more lenient than Swedish courts of justice. Death sentences on grounds of bestiality ended in the 1730s, decades earlier than in Sweden. The sources for the present dissertation include judgment books and Court of Appeal decisions in 253 cases, which show that the persecution of those engaging in bestial acts in 18th century Finland was not organised by the centralised power of Stockholm. There is little evidence of local campaigns that would have been led by authorities. The church in its orthodoxy was losing ground and the clergy governed their parishes with more pragmatism than the Old Testament sanctioned. When exposing bestiality, the legal system was compelled to rely on the initiative of the public. In cases of illicit intercourse or adultery the authorities were even more dependent on the activeness of the local community. Bestiality left no tangible evidence, illegitimate children, to betray the crime to the clergy or secular authorities. The moral views of the church and the local community were not on a collision course. It was a common view that bestiality was a heinous act. Yet nowhere near all crimes came to the authorities' knowledge. Because of the heavy burden of proof, the legal position of the informer was difficult. Passiveness in reporting the crime was partly because most Finns felt it was not their place to intervene in their neighbours' private lives, as long as that privacy posed no serious threat to the neighbourhood. Hidden crime was at least as common as crime more easily exposed and proven. A typical Finnish perpetrator of bestiality was a young unmarried man with no criminal background or mental illness. The suspects were not members of ethnic minorities or marginal social groups. In trials, farmhands were more likely to be sentenced than their masters, but a more salient common denominator than social and economical status was the suspects' young age. For most of the defendants bestiality was a deep-rooted habit, which had been adopted in early youth. This form of subculture spread among the youth, and the most susceptible to experiment with the act were shepherds. The difference between man and animal was not clear-cut or self-evident. The difficulty in drawing the line is evident both in legal sources and Finnish folklore. The law that required that the animal partners be slaughtered led to the killing of thousands of cows and mares, and thereby to substantial material losses to their owners. Regarding bestiality as a crime against property motivated people to report it. The belief that the act would produce human-animal mongrels or that it would poison the milk and the meat horrified the public more than the teachings of the church ever could. Among the most significant aspects in the problems regarding the animals is how profoundly different the worldview of 18th century people was from that of today.

Developmental, functional brain imaging and electrophysiological evidence of visual and auditory working memory

Intact function of working memory (WM) is essential for children and adults to cope with every day life. Children with deficits in WM mechanisms have learning difficulties that are often accompanied by behavioral problems. The neural processes subserving WM, and brain structures underlying this system, continue to develop during childhood till adolescence and young adulthood. With functional magnetic resonance imaging (fMRI) it is possible to investigate the organization and development of WM. The present thesis aimed to investigate, using behavioral and neuroimaging methods, whether mnemonic processing of spatial and nonspatial visual information is segregated in the developing and mature human brain. A further aim in this research was to investigate the organization and development of audiospatial and visuospatial information processing in WM. The behavioral results showed that spatial and nonspatial visual WM processing is segregated in the adult brain. The fMRI result in children suggested that memory load related processing of spatial and nonspatial visual information engages common cortical networks, whereas selective attention to either type of stimuli recruits partially segregated areas in the frontal, parietal and occipital cortices. Deactivation mechanisms that are important in the performance of WM tasks in adults are already operational in healthy school-aged children. Electrophysiological evidence suggested segregated mnemonic processing of visual and auditory location information. The results of the development of audiospatial and visuospatial WM demonstrate that WM performance improves with age, suggesting functional maturation of underlying cognitive processes and brain areas. The development of the performance of spatial WM tasks follows a different time course in boys and girls indicating a larger degree of immaturity in the male than female WM systems. Furthermore, the differences in mastering auditory and visual WM tasks may indicate that visual WM reaches functional maturity earlier than the corresponding auditory system. Spatial WM deficits may underlie some learning difficulties and behavioral problems related to impulsivity, difficulties in concentration, and hyperactivity. Alternatively, anxiety or depressive symptoms may affect WM function and the ability to concentrate, being thus the primary cause of poor academic achievement in children.

Zebrafish as a model of Parkinson's disease

Parkinson’s disease (PD) is the second most common neurodegenerative disease among the elderly. Its etiology is unknown and no disease-modifying drugs are available. Thus, more information concerning its pathogenesis is needed. Among other genes, mutated PTEN-induced kinase 1 (PINK1) has been linked to early-onset and sporadic PD, but its mode of action is poorly understood. Most animal models of PD are based on the use of the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). MPTP is metabolized to MPP+ by monoamine oxidase B (MAO B) and causes cell death of dopaminergic neurons in the substantia nigra in mammals. Zebrafish has been a widely used model organism in developmental biology, but is now emerging as a model for human diseases due to its ideal combination of properties. Zebrafish are inexpensive and easy to maintain, develop rapidly, breed in large quantities producing transparent embryos, and are readily manipulated by various methods, particularly genetic ones. In addition, zebrafish are vertebrate animals and results derived from zebrafish may be more applicable to mammals than results from invertebrate genetic models such as Drosophila melanogaster and Caenorhabditis elegans. However, the similarity cannot be taken for granted. The aim of this study was to establish and test a PD model using larval zebrafish. The developing monoaminergic neuronal systems of larval zebrafish were investigated. We identified and classified 17 catecholaminergic and 9 serotonergic neuron populations in the zebrafish brain. A 3-dimensional atlas was created to facilitate future research. Only one gene encoding MAO was found in the zebrafish genome. Zebrafish MAO showed MAO A-type substrate specificity, but non-A-non-B inhibitor specificity. Distribution of MAO in larval and adult zebrafish brains was both diffuse and distinctly cellular. Inhibition of MAO during larval development led to markedly elevated 5-hydroxytryptamine (serotonin, 5-HT) levels, which decreased the locomotion of the fish. MPTP exposure caused a transient loss of cells in specific aminergic cell populations and decreased locomotion. MPTP-induced changes could be rescued by the MAO B inhibitor deprenyl, suggesting a role for MAO in MPTP toxicity. MPP+ affected only one catecholaminergic cell population; thus, the action of MPP+ was more selective than that of MPTP. The zebrafish PINK1 gene was cloned in zebrafish, and morpholino oligonucleotides were used to suppress its expression in larval zebrafish. The functional domains and expression pattern of zebrafish PINK1 resembled those of other vertebrates, suggesting that zebrafish is a feasible model for studying PINK1. Translation inhibition resulted in cell loss of the same catecholaminergic cell populations as MPTP and MPP+. Inactivation of PINK1 sensitized larval zebrafish to subefficacious doses of MPTP, causing a decrease in locomotion and cell loss in one dopaminergic cell population. Zebrafish appears to be a feasible model for studying PD, since its aminergic systems, mode of action of MPTP, and functions of PINK1 resemble those of mammalians. However, the functions of zebrafish MAO differ from the two forms of MAO found in mammals. Future studies using zebrafish PD models should utilize the advantages specific to zebrafish, such as the ability to execute large-scale genetic or drug screens.

The role of probiotics in Helicobacter pylori infection

Helicobacter pylori (H. pylori) infection is a major cause of chronic gastritis and peptic ulcer disease, and it is also designated as a class-I carcinogen for stomach cancer. The role of probiotics in the treatment of gastrointestinal infections is increasingly documented as an alternative or complement to antibiotics, with the potential to decrease the use of antibiotics or reduce their adverse effects. These studies were conducted to investigate the role of probiotics in the treatment of H. pylori infection. Various aspects included: an investigation of the effects of a probiotic combination consisting of Lactobacillus rhamnosus GG, L. rhamnosus LC705, Propionibacterium freudenreichii ssp. shermanii JS and Bifidobacterium breve Bb99 or B. lactis Bb12 as a supplementation to H. pylori eradication therapy, with special reference to tolerability, effectiveness, and microbiota alterations following the treatment; discovering the role of probiotics in vivo with H. pylori infected and uninfected patients, as well as with an in vitro model of H. pylori infection. The probiotic combination therapy was able to reduce significantly the total symptom score, which takes into account both the frequency and the severity of the adverse effects, during the eradication treatment. The supplementation did not improve the success of the eradication treatment significantly, though some difference was seen in the eradication percentages (91% vs. 79%). The quantities of predominant bacterial groups were altered significantly following the triple treatment. Probiotics slightly counteracted the effects of anti-H. pylori treatment, monitored as significantly less alterations in the total numbers of aerobes and lactobacilli/enterococci group bacteria. After probiotic intervention, L. rhamnosus GG adhered to a minority of the patients upper gastrointestinal mucosa, but all of the probiotics survived well through the gastrointestinal tract transit with and without antimicrobial treatment. Probiotic intervention decreased gastrin-17 levels in H. pylori infected patients and appeared to decrease the 13C-urea breath test values. In in vitro Caco-2 cell line experiments, probiotics inhibited H. pylori adhesion to intestinal epithelial cells. Both L. rhamnosus strains, P. freudenreichii ssp. shermanii JS and the combination inhibited the H. pylori-induced acute cell leakage. Simultaneously, both L.rhamnosus strains and the combination transiently improved the epithelial barrier function. The pro-inflammatory effects prevailed when the probiotics were used in combination. According to this series of studies, probiotic combination could have some potential in reducing adverse effects induced by H. pylori eradication treatment and beneficial effects on H. pylori infected subjects.

Characterization of cytokines, matrix metalloproteinases and toll-like receptors in human periodontal tissue destruction

Periodontal Disease affects the supporting structures of the teeth and is initiated by a microbial biofilm called dental plaque. Severity ranges from superficial inflammation of the gingiva (gingivitis) to extensive destruction of connective tissue and bone leading to tooth loss (periodontitis). In periodontitis the destruction of tissue is caused by a cascade of microbial and host factors together with proteolytic enzymes. Matrix metalloproteinases (MMPs) are known to be central mediators of the pathologic destruction in periodontitis. Initially plaque bacteria provide pathogen-associated molecular patterns (PAMPs) which are sensed by Toll-like receptors (TLRs), and initiate intracellular signaling cascades leading to host inflammation. Our aim was to characterize TNF-α (tumor necrosis factor-alpha) and its type I and II receptors in periodontal tissues, as well as, the effects of TNF-α, IL-1β (interleukin-1beta) and IL-17 on the production and/or activation of MMP-3, MMP-8 and MMP-9. Furthermore we mapped the TLRs in periodontal tissues and assessed how some of the PAMPs binding to the key TLRs found in periodontal tissues affect production of TNF-α and IL-1β by gingival epithelial cells with or without combination of IL-17. TNF-α and its receptors were detected in pericoronitis. Furthermore, increased expression of interleukin-1β and vascular cell adhesion molecule-1 was found as a biological indicator of TNF-α ligand-receptor interaction. MMP-3, -8, and 9 were investigated in periodontitis affected human gingival crevicular fluid and gingival fibroblasts produced pro-MMP-3. Following that, the effect of IL-17 was studied on MMP and pro-inflammatory cytokine production. IL-17 was increased in periodontitis and up-regulated IL-1β, TNF-α, MMP-1 and MMP-3. We continued by demonstrating TLRs in gingival tissues, in which significant differences between patients with periodontitis and healthy controls were found. Finally, enzyme-linked immunosorbent assays were performed to show that the gingival cells response to inflammatory responses in a TLR-dependent manner. Briefly, this thesis demonstrates that TLRs are present in periodontal tissues and present differences in periodontitis compared to healthy controls. The cells of gingival tissues respond to inflammatory process in a TLR-dependent manner by producing pro-inflammatory cytokines. During the destruction of periodontal tissues, the release (IL-1β and TNF-α) and co-operation with other pro-inflammatory cytokines (IL-17), which in turn increase the inflammation and thus be more harmful to the host with the increased presence of MMPs (MMP-1, MMP-3, MMP-8, MMP-9) in diseased over healthy sites.

Cervical headgear in Class II division 1 correction in children : Academic Dissertation

Class II division 1 malocclusion occurs in 3.5 to 13 percent of 7 12 year-old children. It is the most common reason for orthodontic treatment in Finland. Correction is most commonly performed using headgear treatment. The aim of this study was to investigate the effects of cervical headgear treatment on dentition, facial skeletal and soft tissue growth, and upper airway structure, in children. 65 schoolchildren, 36 boys and 29 girls were studied. At the onset of treatment a mean age was 9.3 (range 6.6 12.4) years. All the children were consequently referred to an orthodontist because of Class II division 1 malocclusion. The included children had protrusive maxilla and an overjet of more than 2mm (3 to 11 mm). The children were treated with a Kloehn-type cervical headgear as the only appliance until Class I first molar relationships were achieved. The essential features of the headgear were cervical strong pulling forces, a long upward bent outer bow, and an expanded inner bow. Dental casts and lateral and posteroanterior cephalograms were taken before and after the treatment. The results were compared to a historical, cross-sectional Finnish cohort or to historical, age- and sex-matched normal Class I controls. The Class I first molar relationships were achieved in all the treated children. The mean treatment time was 1.7 (range 0.3-3.1) years. Phase 2 treatments were needed in 52% of the children, most often because of excess overjet or overbite. The treatment decreased maxillary protrusion by inhibiting alveolar forward growth, while the rest of the maxilla and mandible followed normal growth. The palate rotated anteriorly downward. The expansion of the inner bow of the headgear induced widening of the maxilla, nasal cavity, and the upper and lower dental arches. Class II malocclusion was associated with narrower oro- and hypopharyngeal space than in the Class I normal controls. The treatment increased the retropalatal airway space, while the rest of the airway remained unaffected. The facial profile improved esthetically, while the facial convexity decreased. Facial soft tissues masked the facial skeletal convexity, and the soft tissue changes were smaller than skeletal changes. In conclusion, the headgear treatment with the expanded inner bow may be used as an easy and simple method for Class II correction in growing children.

Oral health behaviour, conditions and care among dentate elderly patients in Lithuania: preventive aspects

The present cross-sectional study aimed to assess oral health behaviour, dental and periodontal conditions, dental care, and their relationships among elderly dentate patients in Lithuania. The target population in the study were dentate patients aged 60 and older attending public dental services in Kedainiai, Lithuania. The data collection took place between the autumn of 1999 and the winter of 2001. Data were collected by means of a self-administered questionnaire for all (n=174) and a clinical examination targeting about half of the subjects (n=100). The questionnaire inquired about oral health behaviour, the life-first and also the most recent dental treatments, sources on and self-assessed knowledge of oral self-care, a self-reported number of teeth, and socio-demographic information. The clinical examination included basic dental and periodontal conditions. A total of 82 women and 92 men completed the questionnaire; their mean age was 69.2 and their average number of teeth was 16.2 (CI 95% 15.4-17.1). In all, 25% had 21 or more teeth and 32% indicated wearing removable dentures. The oral health behaviour, the participants reported, was poor: 30% reported twice daily toothbrushing, 57% responded that they always use fluoride toothpaste, 19% indicated daily interdental cleaning, nearly all said they take sugar in their coffee and tea, and 30% indicated going for check-ups. As the main source of information on oral self-care, the subjects indicated health professionals (82%), followed by social contacts (72%), broadcasted media (58%), and printed media (42%). A total of 34% assessed their knowledge of oral self-care as good, and their self-assessed knowledge correlated (r=0.52) with professional guidance they had received about oral self-care. In their most recent treatment, conservative (39%) and non-conservative (34%) treatments dominated, and preventive ones were the least reported (7%). Regarding guidance in oral self-care, 54% reported having received such about toothbrushing, 32% about interdental cleaning, and 33% had been given visual information. Clinical examinations revealed the presence of plaque, calculus, bleeding on probing and deepened pockets in all of the subjects; 70% of the subjects were diagnosed with pockets of 6mm and deeper, 94% with caries, and 73% with overhangs of restorations. Those subjects assessing their knowledge of oral self-care as good and reporting a higher intensity of guidance in oral self-care as received, indicated practicing the recommended oral self-care more frequently. Twice daily toothbrushing was associated with good self-assessed knowledge of oral self-care (OR 4.1, p<0.001) and a university education (OR 5.6, p<0.001). Those subjects with better oral health behaviour had a greater number of teeth. Having 21 or more teeth was associated with good self-assessed knowledge of oral self-care (OR 4.1, p=0.03). Better periodontal conditions were associated with a higher frequency of toothbrushing. The presence of periodontal pockets of 6mm and deeper was associated with the level of self-assessed knowledge of oral self-care being below good (OR=3.0, p=0.04) and the level of dental cleanliness being poor (OR=2.7, p=0.02). To conclude, oral health behaviour and conditions call for improvement in elderly subjects in Lithuania. To improve the oral health of their elderly dentate patients, dentists should apply all the available tools of chair-side prevention and active guidance. The latter would be an effective means of updating the knowledge of oral self-care and supporting recommended oral health behaviour. A preventive approach should be strongly emphasized in countries with limited resources for oral health care, such as Lithuania. Author’s address: Sonata Vyšniauskaite, Department of Oral Public Health, Institute of Dentistry, University of Helsinki, P.O.Box 41, FI-00014 Helsinki, Finland. E-mail: sonata.vysniauskaite@helsinki.fi

Drug Analysis without Primary Reference Standards : Application of LC-TOFMS and LC-CLND to Biofluids and Seized Material

Drug Analysis without Primary Reference Standards: Application of LC-TOFMS and LC-CLND to Biofluids and Seized Material Primary reference standards for new drugs, metabolites, designer drugs or rare substances may not be obtainable within a reasonable period of time or their availability may also be hindered by extensive administrative requirements. Standards are usually costly and may have a limited shelf life. Finally, many compounds are not available commercially and sometimes not at all. A new approach within forensic and clinical drug analysis involves substance identification based on accurate mass measurement by liquid chromatography coupled with time-of-flight mass spectrometry (LC-TOFMS) and quantification by LC coupled with chemiluminescence nitrogen detection (LC-CLND) possessing equimolar response to nitrogen. Formula-based identification relies on the fact that the accurate mass of an ion from a chemical compound corresponds to the elemental composition of that compound. Single-calibrant nitrogen based quantification is feasible with a nitrogen-specific detector since approximately 90% of drugs contain nitrogen. A method was developed for toxicological drug screening in 1 ml urine samples by LC-TOFMS. A large target database of exact monoisotopic masses was constructed, representing the elemental formulae of reference drugs and their metabolites. Identification was based on matching the sample component s measured parameters with those in the database, including accurate mass and retention time, if available. In addition, an algorithm for isotopic pattern match (SigmaFit) was applied. Differences in ion abundance in urine extracts did not affect the mass accuracy or the SigmaFit values. For routine screening practice, a mass tolerance of 10 ppm and a SigmaFit tolerance of 0.03 were established. Seized street drug samples were analysed instantly by LC-TOFMS and LC-CLND, using a dilute and shoot approach. In the quantitative analysis of amphetamine, heroin and cocaine findings, the mean relative difference between the results of LC-CLND and the reference methods was only 11%. In blood specimens, liquid-liquid extraction recoveries for basic lipophilic drugs were first established and the validity of the generic extraction recovery-corrected single-calibrant LC-CLND was then verified with proficiency test samples. The mean accuracy was 24% and 17% for plasma and whole blood samples, respectively, all results falling within the confidence range of the reference concentrations. Further, metabolic ratios for the opioid drug tramadol were determined in a pharmacogenetic study setting. Extraction recovery estimation, based on model compounds with similar physicochemical characteristics, produced clinically feasible results without reference standards.

Early-onset depressive disorders,related mental health disorders and substance use-A prospective : longitudinal study of Finnish twins born 1983-1987

Early-onset psychiatric illnesses effects scatter to academic achievements as well as functioning in familial and social environments. From a public health point of view, depressive disorders are the most significant mental health disorders that begin in adolescence. Using prospective and longitudinal design, this study aimed to increase the understanding of early-onset depressive disorders, related mental health disorders and developing substance use in a large population-derived sample of adolescent Finnish twins. The participants of this study, FinnTwin12, an ongoing longitudinal population-based study, came from Finnish families with twins born in 1983-87 (exhaustive of five birth cohorts, identified from Finland s Central Population Register). With follow-up ongoing at age 20-24, this thesis assessed adolescent mental health in the first three waves, starting from baseline age 11-12 to follow-ups at age 14 and 17½. Some 5600 twins participated in questionnaire assessments of a wide range of health related behaviors. Mental health was further assessed among an intensively studied subsample of 1852 adolescents, who completed also professionally administered interviews at age 14, which provided data for full DSM-IV/III-R (Diagnostic and Statistical Manual for Mental Health disorders, 4th and 3rd editions) diagnoses. The participation rates of the study were 87-92%. The results of the study suggest, that the diagnostic criteria for major depressive disorder (MDD) may not capture youth with clinically significant early-onset depressive conditions outside clinical settings. Milder cases of depression, namely adolescents fulfilling the diagnostic criteria for minor depressive disorder, a qualitatively similar condition to MDD with fewer symptoms are also associated with marked suicidal thoughts, plans and attempts, recurrences and a high degree of comorbidity. Prospectively and longitudinally, early-onset depressive disorders were of substantial importance in the context of other mental health disorders and substance use behaviors: These data from a large population-derived sample established a substantial overlap between early-onset depressive disorders and attention deficit hyperactivity disorder in adolescent females, both of them significantly predictive for development of substance use among girls. Only in females baseline DSM-IV ADHD symptoms were strong predictors of alcohol abuse and dependence and illicit drug use at age 14 and frequent alcohol use and illicit drug use at age 17.½ when conduct disorder and previous substance use were controlled for. Early-onset depressive disorders were also prospectively and longitudinally associated to daily smoking behavior, smokeless tobacco use, frequent alcohol use and illicit drug use and eating disorders. Analysis of discordant twins suggested that these predictive associations were independent of familial confounds, such as family income, structure and parental models. In sum, early-onset depressive disorders predict subsequent involvement of substance use and psychiatric morbidity. A heightened risk for substance use is substantial also among those depressed below categorical diagnosis of MDD. Whether early recognition and interventions among these young people hold potential for substance use prevention further in their lives has potential public health significance and calls for more research. Data from this population-derived sample with balanced representation of boys and girls, suggested that boys and girls with ADHD behaviors may differ from each other in their vulnerability to substance use and depressive disorders: the data suggest more adverse substance use outcome for girls that was not attenuated by conduct disorder or previous substance use. Further, the prospective associations of early-onset depressive disorders and future elevated levels of addictive substance use is not explained by familial factors supporting future substance use, which could have important implications for substance use prevention.

High-density lipoprotein 17beta-estradiol fatty acyl esters and phytoestrogens : Impact on reverse cholesterol transport and women's cardiovascular health

Reverse cholesterol transport (RCT) is an important function of high-density lipoproteins (HDL) in the protection of atherosclerosis. RCT is the process by which HDL stimulates cholesterol removal from peripheral cells and transports it to the liver for excretion. Premenopausal women have a reduced risk for atherosclerosis compared to age-matched men and there exists a positive correlation for serum 17β-estradiol (E2) and HDL levels in premenopausal women supporting the role of E2 in atherosclerosis prevention. In premenopausal women, E2 associates with HDL as E2 fatty acyl esters. Discovery of the cellular targets, metabolism, and assessment of the macrophage cholesterol efflux potential of these HDL-associated E2 fatty acyl esters were the major objectives of this thesis (study I, III, and IV). Soy phytoestrogens, which are related to E2 in both structure and function, have been proposed to be protective against atherosclerosis but the evidence to support these claims is conflicting. Therefore, another objective of this thesis was to assess the ability of serum from postmenopausal women, treated with isoflavone supplements (compared to placebo), to promote macrophage cholesterol efflux (study II). The scope of this thesis was to cover the roles that HDL-associated E2 fatty acyl esters have in the cellular aspects of RCT and to determine if soy isoflavones can also influence RCT mechanisms. SR-BI was a pivotal cellular receptor, responsible for hepatic and macrophage uptake and macrophage cholesterol efflux potential of HDL-associated E2 fatty acyl esters. Functional SR-BI was also critical for proper LCAT esterification activity which could impact HDL-associated E2 fatty acyl ester assembly and its function. In hepatic cells, LDL receptors also contributed to HDL-associated E2 fatty acyl esters uptake and in macrophage cells, estrogen receptors (ERs) were necessary for both HDL-associated E2 ester-specific uptake and cholesterol efflux potential. HDL-containing E2 fatty acyl esters (E2-FAE) stimulated enhanced cholesterol efflux compared to male HDL (which are deficient in E2) demonstrating the importance of the E2 ester in this process. To support this, premenopausal female HDL, which naturally contains E2, showed greater macrophage cholesterol efflux compared to males. Additionally, hepatic and macrophage cells hydrolyzed the HDL-associated E2 fatty acyl ester into unesterified E2. This could have important biological ramifications because E2, not the esterified form, has potent cellular effects which may influence RCT mechanisms. Lastly, soy isoflavone supplementation in postmenopausal women did not modulate ABCA1-specific macrophage cholesterol efflux but did increase production of plasma pre-β HDL levels, a subclass of HDL. Therefore, the impact of isoflavones on RCT and cardiovascular health needs to be further investigated. Taken as a whole, HDL-associated E2 fatty acyl esters from premenopausal women and soy phytoestrogen treatment in postmenopausal women may be important factors that increase the efficiency of RCT through cellular lipoprotein-related processes and may have direct implications on the cardiovascular health of women.